EFFECTS OF 5-HT1A RECEPTOR AGONISTS AND NMDA RECEPTOR ANTAGONISTS IN THE SOCIAL-INTERACTION TEST AND THE ELEVATED PLUS MAZE
EFFECTS OF 5-HT1A RECEPTOR AGONISTS AND NMDA RECEPTOR ANTAGONISTS IN THE SOCIAL-INTERACTION TEST AND THE ELEVATED PLUS MAZE
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DOI：
10.1016/0014-2999(89)90811-x
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发表时间：
1989-10-04
影响因子：
5
通讯作者：
FIELDING, S
中科院分区：
文献类型：
--
作者：
DUNN, RW;CORBETT, R;FIELDING, S
几种5-HT 1A激动剂和兴奋性氨基酸拮抗剂的效果进行了比较，标准苯二氮卓类药物，地西泮和利血平（CDP）在两个试验预测抗焦虑活性，社会互动和高架十字迷宫程序。5-HT 1A激动剂、丁螺环酮、吉哌隆和8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）的抗焦虑作用的指示剂均分别显著增加了社交互动和高架十字迷宫程序中的社交互动时间和开放臂探索时间。同样，在这些试验中，抗焦虑活性也由竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂产生。2-氨基-5-膦酰基戊酸（AP-5）、2-氨基-7-膦酰基庚酸（AP-7）、3-（2-羧基哌嗪-4-基）-丙基-1-膦酸（CPP）和非竞争性NMDA拮抗剂（+）-5-甲基-10，11-二氢-5H-二苯并[a，d]环庚烯-5，10-亚胺（MK-801）。此外，这些药物的抗焦虑作用与苯二氮卓类药物相同。这两类化合物在育亨宾诱导的癫痫发作试验中进行了区分，NMDA拮抗剂剂量依赖性拮抗癫痫发作，类似于苯二氮卓类，而5-HT 1A激动剂无活性。这些结果表明，5-HT 1A激动剂和NMDA拮抗剂可能是潜在的非经典抗焦虑剂，具有不同的作用机制。
The effects of several 5-HT1A agonists and excitatory amino acid antagonists were compared to the standard benzodiazepines, diazepam and chlordiazepoxide (CDP) in two assays predictive of anxiolytic activity, the social interaction and elevated plus maze procedures. Indicative of anxiolytic effects the 5-HT1A agonists, buspirone, gepirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) all significantly increased social interaction time and open arm exploration time in the social interaction and elevated plus maze proceduers, respectively. Likewise, anxiolytic activity in these assays were also produced by the competitive N-methyl-D-aspartate (NMDA) antagonists. 2-amino-5-phosphonoavaleric acid (AP-5), 2-amino-7-phosphonoheptanoic acid (AP-7), 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the non-competitive NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) while NMDA produced anxiogenic effects. Furthermore, the anxiolytic effects of these agents were of equal magnitude to the benzodiazepines. These two classes of compounds were differentiated in the yohimbine-induced seizure assay, with the NMDA antagonists dose dependently antagonizing seizures similar to the benzodiazepines while the 5-HT1A agonists were inactive. These results suggest that the 5-HT1A agonists and the NMDA antagonists may be potential non-classical anxiolytic agents with different mechanisms of action.